Pharmaceutical preparations with a controlled release of a medicinal component have been developed for various purposes such as extending pharmaceutical effects, preventing side effects, and preventing medicinal components from being decomposed by gastric acid. Usually, controlled release oral preparations are mostly formulated into tablets and capsules. Meanwhile, there has recently been a growing need for orally disintegrating tablets that can be taken without water to enhance compliance of elderly patients, patients with dysphagia, and patients who are allowed to take only limited amounts of water.
For example, tamsulosin hydrochloride, which is a drug for urologic diseases, is rapidly absorbed into the body after administration and therefore sustained-release capsules were developed at first to avoid side effects such as orthostatic hypotension. Sustained-release orally disintegrating tablets have been developed therefor and are now commercially available.
When tamsulosin hydrochloride or a like medicinal component the release of which from a pharmaceutical preparation needs to be controlled is formulated as an orally disintegrating tablet, medicinal component-containing fine particles that are designed to release the medicinal component in a controlled manner are produced first and then the fine particles are dispersed in a tablet. From the viewpoint of suppressing a rough texture that is felt upon oral administration, it is desirable to make the particle diameter of controlled-release fine particles that contain a medicinal component as small as possible, and it is generally thought that the upper limit of the average particle diameter is about 350 to about 400 μm.
In general, in the production methods of controlled-release pharmaceutical preparations, a technique by which pharmaceutical preparations such as tablets, granules, and those that contain a medicinal component are coated with a sustained-release film and/or an enteric film is broadly applied to various types of drugs because the operation is simple and the properties of releasing a medicinal component is easily controlled.
When such a coating is applied to particles for an orally disintegrating tablet, coated particles are required to have a very small average particle diameter of less than 400 μm, and therefore it is necessary first to produce medicinal component-containing fine particles that have a shape as spherical as possible, a uniform particle size, and an average particle diameter of less than 250 μm in order to efficiently apply thereto a coating of a high-quality film layer.
The following techniques are known as conventional production methods of medicinal component-containing fine particles.
Patent Literature 1 (JP 62-9A) discloses a technique to obtain medicinal component-containing particles by adding microcrystalline cellulose and a release-controlling agent to tamsulosin hydrochloride and granulating the mixture. The medicinal component-containing particles are applied to a capsule for the sustained-release of tamsulosin hydrochloride. However, the particle size range of the particles is 100 to 1500 μm and there are a considerable number of large particles exceeding 1000 μm are contained, and it is therefore difficult to apply such particles to an orally disintegrating tablet.
Patent Literature 2 (JP 07-165568 A) discloses a method for obtaining medicinal component-containing particles by kneading a mixture of the active ingredient idebenone, crystalline cellulose, and the like, granulating the mixture with an extrusion granulator, and spheronizing the granules with a spheronizer. However, granules that pass through a 60 mesh (i.e., particles smaller than 250 μm) are barely obtained according to this method. The reason for this is easily presumable from the fact that the spheronizer is of a nature not suitable for preparing fine particles smaller than 500 μm.
Patent Literature 3 (JP 06-56700A) discloses a coated core for fine granules obtained by subjecting a principal ingredient and crystalline cellulose to stirring granulation. However, the coated core obtained according to this document has a broad particle size distribution over the 75 to 500 μm range. It may not be possible to provide a coating that enables a highly reproducible release of the medicinal component when coated fine particles for an orally disintegrating tablet, which should have an average particle diameter of no more than about 350 to about 400 μm, are prepared.
Patent Literature 4 (JP 2000-504309 A) discloses a method that performs high-speed stirring granulation on a mixture of a medicinal component and an excipient. However, the obtained granules have a large particle diameter of 500 μm or greater and it is very difficult to apply the granules to an orally disintegrating tablet.
As described above, a technique is not yet established for obtaining medicinal component-containing fine particles that are suitable for an orally disintegrating tablet and that have a sufficiently small particle diameter even after being coated, a uniform particle diameter, and a nearly spherical shape, and therefore demand exists for a method for conveniently obtaining such spherical fine particles.